Our cells have a remarkable kind of software—wetware—that uses the instructions in the DNA in our cells’ nuclei to produce proteins. If you imagine the assembled proteins as a Lego structure, the DNA is like the instruction booklet. But someone has to look at those instructions and put the blocks together in the right way. In the cell, a key part of this process is the messenger RNA: a short-lived, single-strand molecule that carries the instructions from the DNA in the nucleus to the protein-making factory outside it.
In 2020, we figured out how to make messenger RNA with precision, by programming the exact code we wanted, producing it at scale (a printing press for messenger RNA!), and figuring out a way to inject it into people so the fragile mRNA makes it into our cells. The first step was pure programming: Uğur Şahin, the CEO of BioNTech, sat at his computer and entered the genetic code of the spike protein of the mysterious virus that had emerged in Wuhan. Moderna employees had done the same thing the weekend after the genomic sequence was released on January 10. The Moderna vaccine candidate was called mRNA-1273 because it encoded all of the 1,273 amino acids in the SARS-CoV-2 spike protein—the code was so small that it could all be represented with little less than half the number of characters that fit on a single-spaced page.
The rest of the process relied on key scientific and industrial innovations that are quite recent. Messenger RNA are fragile—they disintegrate easily, as they are supposed to. The lipid nanoparticles we envelop them in to use as delivery systems were approved only in 2018. Plus, the viral spike protein is a notorious shape-shifter. It takes one form before it fuses with our cells and another one afterward. The latter, postfusion form did not work well at all for developing vaccines, and scientists only recently figured out how to stabilize a virus’ spike in its prefusion form.